Can Observational Analyses of Routinely Collected Data Emulate Randomized Trials? Design and Feasibility of the Observational Patient Evidence for Regulatory Approval Science and Understanding Disease Project

•Recent emulations of randomized clinical trials (RCTs) with observational data have shown that it is often possible to generate similar treatment effect estimates when the design features of the RCTs can be adequately measured in the observational data.•This article examines the effect of researcher decision making on cohort selection, study design, and selection of statistical methods by 2 study teams independently emulating the same 2 RCTs using a common source data set.•Healthcare decision makers should be aware that researcher decision making is an understudied, but potentially important, potential source of variability across real-world data analyses.